University of Groningen
A multifaceted intervention to reduce guideline non-adherence among prescribing physicians
in Dutch hospitals
Bos, Jacqueline M; Natsch, Stephanie; van den Bemt, Patricia M L A; Pot, Johan L W;
Nagtegaal, J Elsbeth; Wieringa, Andre; van der Wilt, Gert Jan; De Smet, Peter A G M;
Kramers, Cornelis
Published in:
International Journal of Clinical Pharmacy DOI:
10.1007/s11096-017-0553-0
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2017
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Bos, J. M., Natsch, S., van den Bemt, P. M. L. A., Pot, J. L. W., Nagtegaal, J. E., Wieringa, A., van der Wilt, G. J., De Smet, P. A. G. M., & Kramers, C. (2017). A multifaceted intervention to reduce guideline non-adherence among prescribing physicians in Dutch hospitals. International Journal of Clinical Pharmacy, 39(6), 1211-1219. https://doi.org/10.1007/s11096-017-0553-0
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
RESEARCH ARTICLE
A multifaceted intervention to reduce guideline non‑adherence
among prescribing physicians in Dutch hospitals
Jacqueline M. Bos1 · Stephanie Natsch2 · Patricia M. L. A. van den Bemt3 ·
Johan L. W. Pot4 · J. Elsbeth Nagtegaal4 · Andre Wieringa5 · Gert Jan van der Wilt6 ·
Peter A. G. M. De Smet2,7 · Cornelis Kramers1,8
Received: 30 April 2017 / Accepted: 23 October 2017 / Published online: 3 November 2017 © The Author(s) 2017. This article is an open access publication
radiographic contrast agents and surgical antibiotic prophy-laxis was presented to prescribers on the participating wards. Hospital pharmacists performed medication safety consulta-tions, combining medication review of patients who are at risk for drug related problems with visits to ward physicians.
Main outcome measure The outcome measure was the
pro-portion of the admissions of patients in which the physician did not adhere to one or more of the included guidelines. Difference was expressed in odds ratios (OR) with 95% confidence intervals (CI). Multivariable logistic regression analysis was performed. Results 1435 Admissions of 1378 patients during the usual care period and 1195 admissions of 1090 patients during the intervention period were included. Non-adherence was observed significantly less often during the intervention period [21.8% (193/886)] as compared to the usual care period [30.5% (332/1089)]. The adjusted OR was 0.61 (95% CI 0.49–0.76). Conclusion This study shows that education and support of the prescribing physician can reduce guideline non-adherence at surgical wards.
Keywords Education · Guideline adherence · Medication
review · Patient safety · Prescribing · The Netherlands Impacts on practice
• Pharmacotherapeutic guidelines seem to be poorly
imple-mented in daily clinical practice in Dutch hospitals.
• Hospital pharmacists can play a leading role in the
imple-mentation of key pharmacotherapeutic guidelines.
• Education on guidelines and support of the prescribing
physician by the hospital pharmacist are an effective way to improve guideline adherence.
Abstract Background Despite the potential of clinical
practice guidelines to improve patient outcomes, adherence to guidelines by prescribers is inconsistent. Objective The aim of the study was to determine whether an approach of introducing an educational programme for prescribers in the hospital combined with audit and feedback by the hospital pharmacist reduces non-adherence of prescribing physi-cians to key pharmacotherapeutic guidelines. Setting This prospective intervention study with a before–after design evaluated patients at surgical, urological and orthopaedic wards. Method An educational program covering pain man-agement, antithrombotics, fluid and electrolyte manman-agement, prescribing in case of renal insufficiency, application of * Jacqueline M. Bos
jm.bos@cwz.nl
1 Department of Clinical Pharmacy, Canisius Wilhelmina
Hospital, Weg door Jonkerbos 100, 6532 SZ Nijmegen, The Netherlands
2 Department of Pharmacy, Radboud University Medical
Center, Nijmegen, The Netherlands
3 Department of Hospital Pharmacy, Erasmus University
Medical Centre, Rotterdam, The Netherlands
4 Department of Clinical Pharmacy, Meander Medical Centre,
Amersfoort, The Netherlands
5 Department of Clinical Pharmacy, Isala Hospital, Zwolle,
The Netherlands
6 Department of Health Evidence, Radboud University
Medical Centre, Nijmegen, The Netherlands
7 Department Scientific Institute for Quality of Healthcare,
Radboud University Medical Centre, Nijmegen, The Netherlands
8 Department of Clinical Pharmacology and Toxicology,
Radboud University Medical Centre, Nijmegen, The Netherlands
1 3
Introduction
Preventable, clinically relevant problems due to complex pharmacotherapy are common among hospitalised patients [1–4]. Examples are haemorrhage, arterial or venous thrombosis, drug intoxication in renal insufficiency, delir-ium and faecal impaction. Many of these problems derive from prescribing errors that lead to potentially preventable morbidity, mortality and costs [5]. The majority of these are caused by pain medication, antithrombotics, antibacte-rial drugs, cardiovascular drugs, and drugs that are renally excreted [1–3, 6–9].
Different strategies, including introduction of comput-erized physician order entry (CPOE), pharmacist involve-ment on the ward, educational programs and support sys-tems for clinical decision making (CDS) have been studied to address this problem and to improve clinician prescrib-ing in hospitalized patients [10–12].
Clinical practice guidelines with evidence-based recom-mendations for physicians have been developed to assist doctors and to improve patient outcomes. In routine daily practice however, it appears to be difficult to implement key recommendations and guidelines seem to have limited impact on physician prescribing behaviour. Most clinicians can barely keep pace with the rapid advances in pharma-cotherapy. And even if doctors are aware of the guidelines and are willing to change, to alter well established patterns of prescribing is difficult [13]. Earlier research showed that non-compliance to several guidelines by prescribers varies between 33 and 70% [14–16].
Several determinants of practice that prevent or enable guideline adherence, have been described. Guideline fac-tors, such as quality of evidence and accessibility of the guideline, organizational factors and resources, such as the information system, frequent rotations of physicians on the ward and workload, patient factors such as increas-ingly complex multi-morbidity and also individual health professional factors, such as knowledge and skills, aware-ness and professional behaviour play a role [17, 18]. When these factors are taken into account in the development of strategies to improve guideline adherence, the quality of the treatment of hospitalised patients improves [19, 20].
Education is one of the possible strategies to tackle sev-eral of these determinants for non-adherence. Education of prescribers is most effective when it is interactive and con-tinuous, includes discussion of evidence and local consen-sus and when it is followed by feedback on performance. This way of professional development needs to be built into patient care as much as possible, and should prefer-ably take place in real time with clinical decision-support tools and patient-specific reminders to help doctors make the best decisions [21].
The P-REVIEW study is a prospective, multicentre, open intervention study, designed to investigate if an approach of introducing an educational programme for prescribers in the hospital combined with audit and feedback by the hos-pital pharmacist can lead to a clinically relevant benefit for patients at surgical wards [22]. The educational program teaches the prescriber the pharmacological aspects of using high-risk drugs in high-risk patients. The hospital pharma-cist suggests interventions based on a medication review of the patient. Guidelines are an important part of the educa-tional program and the hospital pharmacist actively checks on and improves guideline adherence.
Aim of the study
The aim of the study was to determine whether an approach of introducing an educational programme for prescribers in the hospital combined with audit and feedback by the hospital pharmacist reduces non-adherence of prescribing physicians to key pharmacotherapeutic guidelines.
Ethics approval
The institutional review boards of the Isala Hospital (Zwolle, the Netherlands) and the Meander Medical Centre (Amers-foort, the Netherlands) stated that the study was exempt from ethical approval. Patients’ data were collected and stored in accordance with prevailing privacy regulations.
Methods
Study design and setting
The P-REVIEW study was an open intervention study with a before-after design performed in two large general teach-ing hospitals in the Netherlands (the Isala Hospital (779 beds), and the Meander Medical Centre (600 beds)) [22]. After a 6-month control period (usual care) the intervention was introduced during 3 months. This was followed by a 6-month intervention period. This sub-study on guideline adherence was performed during the fifth month of the usual care period and the fifth month of the intervention period.
Study population
Patients who were admitted to the surgical, urological and orthopaedic wards of the two hospitals during the study period were included. Guideline non-adherence was meas-ured in all these patients. Patients were followed up until
discharge. Patients could be included more than once, in case of readmission in the study period. Day care patients were excluded.
Usual care
During the usual care period the normal procedures of med-ication surveillance and communmed-ication between hospital pharmacists and physicians were maintained. A CPOE and CDS system was applied in both hospitals.
Hospital pharmacists checked medication of all patients on a daily basis with the aid of computer-generated alerts based on a national database (“G-standard”) [23]. They could warn the physician by telephone or in case the advice was less urgent send a an advice on paper to the ward. In both hospitals, pharmacists were supported by a same set of computerised “clinical rules” to screen for specific pre-scribing errors. These clinical rules are based on pharma-cotherapeutic guidelines and combine clinical patient data (like renal function and electrolyte abnormalities) with medication specific factors: dose adjustments in case of renal insufficiency; hypokalemia in patients using diuretic; hyperkalemia in patients using potassium-saving diuretics, ACE inhibitor, trimethoprim or NSAID; hyponatremia in patients using SSRI, thiazide or carbamazepine; folic acid to be added to methotrexate; dosing of oral cytostatics; PPI to be added in case of NSAID [24].
Intervention
During the intervention phase, a combination of an educa-tional program and medication counselling for prescribers on the wards took place.
An educational program covering pain management, antithrombotics, fluid and electrolyte management, pre-scribing in the case of renal insufficiency, application of radiographic contrast agents and surgical antibiotic prophy-laxis was developed. National and local hospital guidelines related to these subjects were also included [25–32]. The program consisted of two parts of approximately 2 h each. All prescribers, who provided medical care on the partici-pating wards during the intervention period, attended the course.
In addition, hospital pharmacists were trained to per-form medication safety consultations (MSC), combining medication reviews and a visit to audit and give feedback to prescribers on the ward by an internist clinical phar-macologist and a hospital pharmacist with specific exper-tise in this area. Medication reviews were performed in high-risk patients, who were identified with a computer-ised screening method. The screening method was based on recent literature on prescription errors and targeted patients at risk for potentially preventable, drug-related
problems. This screening method and a checklist for per-forming medication review on surgical wards is described before by Bos et al. [22]. In the weekly visits of the hospi-tal pharmacist to the physician on the surgical ward, there was special attention for adherence to important pharma-cotherapeutic guidelines that were addressed in the edu-cational program. Feedback was given based on the medi-cation reviews to the prescriber. The attended issues and advices were discussed in a broader context and hospital pharmacists clarified the pharmacological background and related prevailing hospital guidelines.
Guidelines
In order to be able to score guideline non-adherence ten recommended pharmacotherapeutic measures were derived from several guidelines (Table 1).
The guidelines were selected by a group of experts, including hospital pharmacists, clinical pharmacologists and hospital-based physicians in a consensus meeting. The selected guidelines had to relate to medication that has shown to frequently be involved in preventable, clinically relevant, drug-related problems [1–3, 6–8]. All guidelines had to be part of a local implemented protocol in the hospital and were addressed in the educational program.
Study endpoints
The primary outcome measure of guideline non-adherence was the proportion of the admissions of patients in which the physician did not adhere to one or more of the guidelines. The secondary outcome measures were the proportions of admissions of patients in which the physician did not adhere to each of ten guidelines.
Data collection
Collected data included patient characteristics, laboratory and medication data, as well as transfers to other wards, medical correspondence and medical interventions. Data regarding radiology, microbiology, blood transfusion and information about medical incidents were also collected. Part of the requisite data could not be collected automati-cally. Therefore, a trained research assistant collected data manually from the medical records of the patients using a predefined protocol. These data included whether the patient had had surgery, type of surgery and whether the patient had an indication for thrombosis prophylaxis, antibiotics prophy-laxis or endocarditis prophyprophy-laxis.
1 3
Table 1 Phar maco ther apeutic measur es based on pr ev ailing guidelines ACCP Amer ican Colleg e of Ches t Ph ysicians, CBO Dutc h Ins titute f or Healt h Car e Im pr ov ement, DV T deep v ein t hr ombosis, MDRD modification of die t in r enal disease, NHG Dutc h Socie ty of Gener al Pr actitioners, NS AID non-s ter oidal anti-inflammat or y dr ug, NVR Dutc h Association of R adiology , PPI pr ot on pum p inhibit or , SmPC Summar y of Pr oduct Char acter istics, SWA B The Dutc h W or king P ar ty on Antibio tic P olicy , V TE v enous t hr omboembolism Phar maco ther apeutic measur e Effectuation measurement of guideline non-adher
ence Guideline 1. P er ioper ativ e t hr ombosis pr oph ylaxis
All patients under
going sur ger y, wit h a high r isk of t hr ombosis accor ding t o t he guideline, w er e c hec ked whe ther pr ev entiv e ther ap y f or D V T and V TE w as adminis ter ed Diagnos tics, pr ev ention and tr eatment of v enous t hr omboembolism and secondar y pr ev ention of ar ter ial occlusiv e disease (guideline CB O, based on A CCP) [ 25 ] 2. P er ioper ativ e br idging of antit hr ombo tics
All patients under
going sur ger y, using vit amin K ant agonis ts, w er e chec ked whe ther per ioper ativ e br idging of antit hr ombo tics w as
indicated and antit
hr ombo tics w er e adminis ter ed accor ding t o the guideline. Br idging w
as indicated in case of atr
ial fibr illation and a CHADS 2 scor e > 3, r ecent or r ecur rent v enous t hr ombo -embolism, t hr omboembolism due t o t hr ombophilia or mec hani -cal v alv e pr os thesis Diagnos tics, pr ev ention and tr eatment of v enous t hr omboembolism and secondar y pr ev ention of ar ter ial occlusiv e disease (guideline CB O, based on A CCP) [ 25 ]
3. PPI added in case of use of NS
AID
All patients wit
h an ulcer in his tor y and/or an ag e older t han 70 y ears, w er e c hec ked whe ther a pr ot on pum p inhibit or w as added NS
AID use and pr
ev ention of g as tric damag e (guideline CB O) [ 26 ] 4. Lax ativ
e added in case of use of opioid
All patients tr eated wit h an opioid, w er e c hec ked whe ther a lax a-tiv e w as added. P atients wit h a s toma or wit h diagnosed diar -rhoea w er e e xcluded Pain (guideline NHG) [ 27 ], Diagnos tics and tr eatment of pain (guideline Oncoline) [ 28 ] 5. NS AID contr aindicated in im pair ed r enal function
All patients wit
h an im pair ed r enal function (MDRD < 30 ml/ min/1.73 m 2), w er e c hec ked f or NS AID use Dutc h national G-s tandar d [ 23 ] SmPC NS AID [ 29 ] 6. Discontinuation of diur etics in case of r adiocontr as t
All patients who r
eceiv
ed iodinated r
adio-contr
as
t and who used
diur etics, w er e c hec ked whe ther t he diur etic w as discontinued on the da y of t he tes t Pr ecautions f or use of iodinated r adio-contr as t (guideline NVR) [ 30 ] 7. Discontinuation of NS AID in case of r adio-contr as t
All patients who r
eceiv
ed iodinated r
adio-contr
as
t and who used
an NS AID, w er e c hec ked whe ther t he NS AID w as discontinued on t he da y of t he tes t Pr ecautions f or use of iodinated r adio-contr as t (guideline NVR) [ 30 ] 8. Discontinuation of me tfor min in case of r adio-contr as t and im pair ed r enal function
All patients who r
eceiv ed iodinated r adio-contr as t and had im pair ed r
enal function (MDRD < 60 ml/min/1.73 m
2 ) and used me tfor min, w er e c hec ked whe ther me tfor min w as discontinued on t he da y of t he tes t Pr ecautions f or use of iodinated r adio-contr as t (guideline NVR) [ 30 ] 9. P er ioper ativ e antibio tics pr oph ylaxis
All patients under
going sur ger y, wit h an indication f or per ioper a-tiv e antibio tics pr oph ylaxis, w er e c hec ked whe ther pr ev entiv e ther ap y f or inf ection w as adminis ter ed Per ioper ativ e antibio tic pr oph ylaxis (guideline S W AB) [ 31 ] 10. P er ioper ativ e endocar ditis pr oph ylaxis
All patients under
going sur ger y, wit h a high r isk of endocar ditis, wer e c hec ked whe ther pr ev entiv e t her ap y f or endocar ditis w as adminis ter ed Endocar ditis pr oph ylaxis (guideline b y t he N et her land Hear t F oun -dation) [ 32 ]
A validated multisource Microsoft Access database (Microsoft version 2003) was used.
Sample size and data analysis
The PREVIEW-study has been powered on the outcome measure of reduction of clinically relevant, potentially pre-ventable drug-related problems. For the power of this sub-study on guideline adherence, we studied earlier research on this subject showing that non-compliance to several guide-lines by prescribers varies between 33 and 70% [14–16]. Earlier studies that describe interventions that aim to improve guideline adherence showed results on improve-ment of adherence varying form 50–60 to 65–80% [19, 20]. To detect a reduction from 30% adherence to 20% non-adherence, 313 patients had to be included in each group. Because the primary outcome measure of the P-REVIEW study (adverse drug events) needed a very large patient cohort to detect a significant difference, we assumed that measuring during 1 month in both periods would generate enough power for this sub-study on guideline adherence.
Baseline characteristics were presented as means and standard deviation or percentages for continuous or dichoto-mous outcomes, respectively.
Differences between groups were expressed in odds ratios with 95% confidence intervals and were tested for statisti-cal significance using independent t test or Chi square tests, as appropriate. P < 0.05 was considered to be statistically significant.
In order to correct for possible confounding, multivari-able logistic regression analysis was performed. The fol-lowing possible confounders were initially entered into the model: age, gender, department of admission, number of medicines on the first day after admission and pharmaco-therapeutic group of these medicines, length of stay and renal function. Those that showed no clear relation with the outcome (p > 0.10) were removed, but only in case their removal did not alter the relation under study (OR on non-adherence in usual care period vs intervention period) by more than 10%.
Statistical analyses were performed using SPSS Statistics version 22 (IBM Software, New York).
Results
In the usual care period of the study 1435 admissions (1378 patients) and in the intervention period 1195 admissions (1090 patients) were included.
Table 2 details the characteristics of these patients. There was no difference between the two groups in age, gender, department of admission or in the number of medications on
the first day after admission. Also, there was no difference in use of medication, length of hospital stay and the proportion of patients with renal insufficiency.
Table 3 shows the proportions of admissions of patients in which the physician did not adhere to the guidelines in the usual care period and in the intervention period, respectively. In 1089 admissions of 1069 patients in the usual care period and in 886 admissions of 864 patients in the intervention period, one or more included guidelines were applicable.
Figure 1 shows a forest plot in which the odds ratios for
non-adherence are presented.
A significantly lower proportion of admissions of patients in which the physician did not adhere to the pre-vailing guidelines occurred in the intervention period (21.8% (193/886) compared to the usual care period [30.5% (332/1089)] (p < 0.05). The odds ratio (OR) was 0.64 (95% CI 0.52–0.78).
After correction for possible confounders, the adjusted OR was 0.61 (95% CI 0.49–0.76).
When the analysis was conducted with protocol non-adherence as denominator (total number of times that a guideline had to be followed by a prescriber) instead of admissions, results were comparable. [13.5% (211/1564) in the intervention period compared to 18.6% (368/1976) in the usual care period (p ≤ 0.05)]. The odds ratio (OR) was 0.68 (95% CI 0.57–0.82).
Discussion
Our study shows that education and support of the prescrib-ing physician with respect to high-risk patients in surgical departments can lead to reduced pharmacotherapeutic guide-line non-adherence among prescribing physicians. Achieved effects were obtained on top of the effect of other measures as CPOE/CDS system and clinical rules, which were part of usual care.
Earlier studies describe interventions that aim to improve guideline adherence in the hospital. Hogli et al. describe an intervention study, reporting distribution of a recently pub-lished pocket version of the national guideline. This led to a substantial increase in prescribing of appropriate empirical antibiotics from 61.7 to 83.8% [20]. Schouten et al. imple-mented a multifaceted guideline-implementation strategy, considering the barriers of implementation of guidelines. They found an increase of the rate of guideline adherence of antibiotic prescription from 50.3 to 64.3% [19].
In the two hospitals that participated in this study, the guidelines targeted in our study had already been imple-mented. Nevertheless, we found that in nearly one third of cases physicians were non-adherent to the local hospi-tal guidelines. This is in line with earlier research on this subject. Van den Bemt et al. found that the proportion of
1 3
admissions not compliant with guidelines on gastric protec-tion in case of use of NSAID in hospitalized surgical patients was 46.6% [16]. Drenth et al. found an adherence of 53.9% with a dosing guideline in patients with impaired renal func-tion at hospital discharge [15]. Schilp et al. studied adher-ence to the guideline concerning identification and hydration of high-risk patients for contrast-induced nephropathy in dif-ferent hospitals and found that only two third of the high-risk patients were hydrated before contrast administration [33]. Huijts et al. reported proportions of patients receiving guideline-adherent antibiotics for community acquired pneu-monia from 30.5 to 62.9% [34].
Educating prescribers is a measure that can be taken on top of other measures to improve guideline adherence. Edu-cating prescribers is only effective if it is a part of a multi-faceted intervention [35]. Novel of the P-REVIEW educa-tion program is the combinaeduca-tion with a weekly visit by the
hospital pharmacist, who audited and improved guideline adherence. We aimed to boost the effect of the education program by the weekly visits of the hospital pharmacist. We previously showed that these weekly visits were feasi-ble and also efficient. We hypothesized that the support by education of the prescriber by the hospital pharmacist in a more pro-active role is more efficient and effective than the traditional retrospective role of the hospital pharmacist in medication surveillance [22]. In this study we show that this intervention can lead to a significant decrease in non-adherence of guidelines, although there may be still room for improvement.
The study has several strengths.
The study was performed in two representative general teaching hospitals. The intervention was easily implemented, since both education and weekly visits were performed by Table 2 Characteristics of admitted patients
LMWH low molecular weight heparin, RAS renin angiotensin system, NSAIDs non-steroidal anti-Inflammatory drugs
Usual care period Intervention period p value
No. of admissions 1435 1195
No. of patients 1378 1090
Mean age of patients in years ± SD 63.8 ± 17.2 63.3 ± 17.1 0.406
Gender of patients, n (%) female 720 (50.2%) 599 (50.1%) 0.980
Department of admission 0.605
General surgery, n (%) 852 (59.4%) 682 (57.1%)
Orthopaedic surgery, n (%) 328 (22.9%) 294 (24.6%)
Urology, n (%) 255 (17.8%) 219 (18.3%)
Mean no. of medications the first day after admission, ± SD 6.9 ± 5.5 7.2 ± 5.8 0.233
Medication the first day after admission, n (%)
Hypoglycemics 178 (12.4%) 156 (13.1%) 0.618
Vitamin K antagonists 149 (10.4%) 117 (9.8%) 0.616
Heparin/LMWH 951 (66.3%) 773 (64.7%) 0.394
Thrombocyte aggregation inhibitors 284 (19.8%) 238 (19.9%) 0.936
Diuretics 337 (23.5%) 287 (24.0%) 0.749
Beta blockers 391 (27.2%) 305 (25.5%) 0.318
Calcium channel blockers 146 (10.2%) 142 (11.9%) 0.162
RAS inhibitors 375 (26.1%) 317 (26.5%) 0.819
NSAIDs 485 (33.8%) 424 (35.5%) 0.366
Opioids 601 (41.9%) 491 (41.1%) 0.681
Antipsychotics 90 (6.3%) 79 (6.6%) 0.724
Mean length of stay, days ± SD
General surgery 7.7 ± 9.7 7.0 ± 8.3 0.154
Orthopaedic surgery 7.6 ± 8.6 6.7 ± 6.5 0.107
Urology 4.3 ± 4.8 4.4 ± 4.1 0.798
MDRD eGFR of patients (ml/min/1.73 m2), n (%) (n = 1016*) (n = 836*) 0.476
< 10 4 (0.4%) 1 (0.1%)
10–30 43 (4.2%) 39 (4.7%)
30–60 227 (22.3%) 203 (24.3%)
health care providers already active in the hospital and the intervention did not lead to additional costs.
The intervention combines different strategies. These strategies address different factors that have been described to impair quality of care and can influence guideline adher-ence [17].
By educating the prescriber in the hospital and teaching the prescriber during medication safety consultation, the knowledge and skills needed to adhere to guidelines will improve. Also the attitude towards guidelines in general and motivation to adhere may improve. This study how-ever, didn’t collect qualitative data from the prescribers to
support this hypothesis, and this would be useful to integrate in future research.
These weekly visits of the hospital pharmacist can be considered as a continuous form of workplace-based educa-tion. This addresses the problem that a short-term education programme has been found to have only a transient effect on the frequency of prescribing errors [36].
There are some limitations as well. We selected ten rel-evant pharmacotherapeutic measures derived from several guidelines. This selection was not complete, and our results may not be generalisable to other or all guidelines. Also, the study was performed in two hospitals, which might limit the external validity of the study.
Table 3 Non-adherence of prescribers to pharmacotherapeutic measures based on prevailing guidelines
a OR, adjusted for confounders b Statistical significant
Usual care period (n = 1435) Interven-tion period (n = 1195)
Odds ratios and con-fidence intervals
Non-adherence Non-adherence OR 95% CI
1. Perioperative thrombosis prophylaxis if indicated? 22/590 (3.7%) 10/490 (2.0%) 0.54 0.25–1.15 2. Perioperative bridging of antithrombotics if indicated? 2/48 (4.2%) 2/46 (4.3%) 1.05 0.14–7.75
3. In case of NSAID use, ppi added if indicated? 5/101 (5.0%) 3/83 (3.6%) 0.72 0.17–3.11
4. In case of opioid use, laxative added if indicated? 154/296 (52%) 62/190 (32.6%) 0.45b 0.31–0.65
5. In case of impaired renal function (MDRD < 30), no use of NSAID? 8/50 (16.0%) 4/40 (10.0%) 0.54 0.15–1.94 6. In case of radiocontrast, diuretics discontinued? 16/23 (69.6%) 20/29 (69.0%) 0.97 0.30–3.18 7. In case of radiocontrast, NSAID discontinued? 17/25 (68.0%) 15/20 (75.0%) 1.41 0.38–5.26 8. In case of radiocontrast and MDRD < 60, metformin discontinued? 2/3 (66.7%) 2/2 (100.0%) 0.33 0.01-12.79 9. Perioperative antibiotics prophylaxis, if indicated? 136/832 (16.3%) 93/661 (14.1%) 0.84 0.63–1.12 10. Perioperative endocarditis prophylaxis, if indicated? 6/8 (75%) 0/3 (0%) 0.05 0.00–1.50
Overall non-adherence 332/1089 (30.5%) 193/886 (21.8%) 0.64b 0.52–0.78
0.61a,b 0.49–0.76
Fig. 1 Forest plot of non-adher-ence of prescribers to pharma-cotherapeutic measures based on prevailing guidelines
1 3
This study was not a randomised controlled study, but was performed in a before after design, introducing the possibil-ity of confounding. Therefore, to adjust for confounding, we performed a multivariable logistic regression analysis. Yet, we may not have identified all potential confounders.
We defined the outcome measure as the proportion of the admissions of patients in which the physician did not adhere to one or more of the guidelines. We assumed that in every single admission a physician has to follow all guidelines. When a patient is readmitted, the treating phy-sician is often different and guidelines can be different from an early admission of the patient. On the other hand adherence on guidelines in an early admission can lead to (not intended) adherence in a readmission.
For each guideline we only included these cases in which there was no possible discussion on adherence (Table 1). By specifying the cases, we minimized the pos-sibility of intended non-adherence by the physician.
The P-REVIEW study describes 106 admissions with one or more clinically relevant, potentially preventable, drug-related events in the usual care period and 73 in the intervention period [22]. These drug-related events are divided into different types of events, such as haemor-rhage, thrombosis, renal failure related events, central nervous systems events, faecal impaction, hypoventilation and a group of unclassifiable events [22]. We noted that 25 of the 106 events in the usual care period and 15 of the 73 events in the intervention period relate to the studied guidelines and could possibly have been prevented in case of better guideline adherence. That means that only a mod-est part of the positive effect on these events can be related to an improvement in adherence of the studied guidelines.
This suggests that improving guideline adherence will have only limited effect and it may not be necessary to pursue 100% adherence. It may be better not to focus on guideline adherence or implementation of clinical rules alone, but on a comprehensive medication review of high risk patients, in which a check on adherence of guidelines and clinical rules is integrated.
Given the limited resources in healthcare, we think this could be an important question for future research.
Conclusions
In summary, this study shows that education and support of the prescribing physician with respect to high-risk patients in surgical departments leads to an improvement of guideline adherence among prescribing physicians. Acknowledgements We would like to express our gratitude to the hospital pharmacists and to the physicians of the surgical, orthopaedic
surgical and urological wards of the Meander Medical Centre in Amersfoort and the Isala Hospital in Zwolle. Also we thank Hans Groenewoud, (Department of Health Evidence, Radboud university medical centre, Nijmegen, the Netherlands) statistical expert, for his advice in data analysis.
Funding This study was financially supported by the Netherlands Organisation for Health Research and Development (ZonMw Grant 171101004), by the Royal Dutch Society of Pharmacists (KNMP) and by the Dutch insurance company UVIT. The funders had no role in study design, in collection, analysis and interpretation of data nor the writing of the report.
Conflicts of interest The authors declare that they have no conflicts of interests.
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://crea-tivecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appro-priate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
References
1. Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, Pirmohamed M. Adverse drug reactions in hospital in-patients: a prospective analysis of 3695 patient-episodes. PLoS ONE. 2009;4(2):e4439.
2. Hoonhout LH, de Bruijne MC, Wagner C, Asscheman H, van der Wal G, van Tulder MW. Nature, occurrence and conse-quences of medication-related adverse events during hospitaliza-tion: a retrospective chart review in the Netherlands. Drug Saf. 2010;33(10):853–64.
3. Krahenbuhl-Melcher A, Schlienger R, Lampert M, Haschke M, Drewe J, Krahenbuhl S. Drug-related problems in hospitals: a review of the recent literature. Drug Saf. 2007;30(5):379–407. 4. Miguel A, Azevedo LF, Araujo M, Pereira AC. Frequency
of adverse drug reactions in hospitalized patients: a system-atic review and meta-analysis. Pharmacoepidemiol Drug Saf. 2012;21(11):1139–54.
5. Passarelli MC, Jacob-Filho W, Figueras A. Adverse drug reactions in an elderly hospitalised population: inappropriate prescription is a leading cause. Drugs Aging. 2005;22(9):767–77.
6. Eppenga WL, Kramers C, Derijks HJ, Wensing M, Wetzels JF, De Smet PA. Drug therapy management in patients with renal impair-ment: how to use creatinine-based formulas in clinical practice. Eur J Clin Pharmacol. 2016;72(12):1433–9.
7. Klopotowska JE, Wierenga PC, Stuijt CC, Arisz L, Dijkgraaf MG, Kuks PF, et al. Adverse drug events in older hospitalized patients: results and reliability of a comprehensive and structured identifi-cation strategy. PLoS ONE. 2013;8(8):e71045.
8. Saedder EA, Brock B, Nielsen LP, Bonnerup DK, Lisby M. Iden-tifying high-risk medication: a systematic literature review. Eur J Clin Pharmacol. 2014;70(6):637–45.
9. Boeker EB, Ram K, Klopotowska JE, de Boer M, Creus MT, de Andres AL, et al. An individual patient data meta-analysis on factors associated with adverse drug events in surgical and non-surgical inpatients. Br J Clin Pharmacol. 2015;79(4):548–57. 10. Keers RN, Williams SD, Cooke J, Walsh T, Ashcroft DM.
administration errors in hospitals: a systematic review. Drug Saf. 2014;37(5):317–32.
11. Manias E, Kinney S, Cranswick N, Williams A, Borrott N. Inter-ventions to reduce medication errors in pediatric intensive care. Ann Pharmacother. 2014;48(10):1313–31.
12. Manias E, Williams A, Liew D. Interventions to reduce medica-tion errors in adult intensive care: a systematic review. Br J Clin Pharmacol. 2012;74(3):411–23.
13. Grol R, Grimshaw J. From best evidence to best practice: effective implementation of change in patients’ care. Lancet. 2003;362(9391):1225–30.
14. Chen Y, Sloan FA, Yashkin AP. Adherence to diabetes guidelines for screening, physical activity and medication and onset of com-plications and death. J Diabetes Complicat. 2015;29(8):1228–33. 15. Drenth-van Maanen AC, van Marum RJ, Jansen PA, Zwart JE,
van Solinge WW, Egberts TC. Adherence with dosing guideline in patients with impaired renal function at hospital discharge. PLoS ONE. 2015;10(6):e0128237.
16. van den Bemt PM, Chaaouit N, van Lieshout EM, Verhofstad MH. Noncompliance with guidelines on proton pump inhibitor prescription as gastroprotection in hospitalized surgical patients who are prescribed NSAIDs. Eur J Gastroenterol Hepatol. 2016;28(8):857–62.
17. Flottorp SA, Oxman AD, Krause J, Musila NR, Wensing M, Godycki-Cwirko M, et al. A checklist for identifying determi-nants of practice: a systematic review and synthesis of frameworks and taxonomies of factors that prevent or enable improvements in healthcare professional practice. Implement Sci. 2013;8:35. 18. Schouten JA, Hulscher ME, Natsch S, Kullberg BJ, van der Meer
JW, Grol RP. Barriers to optimal antibiotic use for community-acquired pneumonia at hospitals: a qualitative study. Qual Saf Health Care. 2007;16(2):143–9.
19. Schouten JA, Hulscher ME, Trap-Liefers J, Akkermans RP, Kull-berg BJ, Grol RP, et al. Tailored interventions to improve antibi-otic use for lower respiratory tract infections in hospitals: a cluster-randomized, controlled trial. Clin Infect Dis. 2007;44(7):931–41. 20. Hogli JU, Garcia BH, Skjold F, Skogen V, Smabrekke L. An audit
and feedback intervention study increased adherence to antibiotic prescribing guidelines at a Norwegian hospital. BMC Infect Dis. 2016;16:96.
21. Eddy K, Jordan Z, Stephenson M. Health professionals’ expe-rience of teamwork education in acute hospital settings: a sys-tematic review of qualitative literature. JBI Database Syst Rev Implement Rep. 2016;14(4):96–137.
22. Bos JM, van den Bemt PM, Kievit W, Pot JL, Nagtegaal JE, Wier-inga A, et al. A multifaceted intervention to reduce drug-related
complications in surgical patients. Br J Clin Pharmacol. 2017;83(3):664–77.
23. Dutch National G-standard [Internet]. Z-index; 2017. www.z-index.nl.
24. Rommers MK, Zwaveling J, Guchelaar HJ, Teepe-Twiss IM. Evaluation of rule effectiveness and positive predictive value of clinical rules in a Dutch clinical decision support system in daily hospital pharmacy practice. Artif Intell Med. 2013;59(1):15–21. 25. Diagnostics, prevention and treatment of venous thromboem-bolism and secondary prevention of arterial occlusive disease (guideline CBO, based on ACCP) [Internet]. CBO;2009. https:// cvgk.nl/legacy/block/bestanden/CBO-richtlijn-Stolling-2009.pdf. 26. NSAID use and prevention of gastric damage (guideline CBO)
[Internet]. CBO; 2003. https://www.mdl.nl/sites/www.mdl.nl/files/ richlijnen/NSAID-gebruik_en_preventie_van_maagschade_-_ CBO_2003.pdf.
27. Pain (guideline NHG) [Internet]. NHG; 2016. www.nhg.org. 28. Diagnostics and treatment of pain [Internet]. Oncoline, 2016.
www.oncoline.nl.
29. SmPC NSAID [Internet]. CBG-MEB, 2017. https://www.cbg-meb.nl/geneesmiddeleninformatiebank.
30. Precautions for use of iodinated radio-contrast (guideline NVR) [Internet]. CBO; 2007. https://www.mdl.nl/sites/www.mdl.nl/ files/richlijnen/Richtlijn_Voorzorgsmaatregelen_bij_jodiumhou-dende_contrastmiddelen.pdf.
31. Perioperative antibiotic prophylaxis (guideline SWAB) [Internet]. SWAB; 2017. http://www.swab.nl.
32. Endocarditis prophylaxis (guideline SWAB) [Internet]. SWAB; 2017. http://www.swab.nl.
33. Schilp J, de Blok C, Langelaan M, Spreeuwenberg P, Wagner C. Guideline adherence for identification and hydration of high-risk hospital patients for contrast-induced nephropathy. BMC Nephrol. 2014;15:2.
34. Huijts SM, van Werkhoven CH, Boersma WG, Buijs J, Buunk G, Compaijen CJ, et al. Guideline adherence for empirical treatment of pneumonia and patient outcome. Treating pneumonia in the Netherlands. Neth J Med. 2013;71(10):502–7.
35. Bos JM, van den Bemt PM, De Smet PA, Kramers C. The effect of prescriber education on medication related patient harm in the hospital: a systematic review. Br J Clin Pharmacol. 2017;83(5):953–61.
36. Peeters MJ, Pinto SL. Assessing the impact of an educational program on decreasing prescribing errors at a university hospital. J Hosp Med. 2009;4(2):97–101.
